Collagen fiber ribbons with integrated fixation sutures and methods of making the same

ABSTRACT

The disclosure describes implantable bioprosthesis and constructs having an implantable woven ribbon with at least one integrated suture.

RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.15/466,299, filed Mar. 22, 2017, which is a divisional of U.S. patentapplication Ser. No. 14/003,484, filed Mar. 5, 2014, now U.S. Pat. No.9,636,209, issued May 2, 2017, which is a 35 USC § 371 national phaseapplication of PCT/US2012/027366, International Filing Date Mar. 2,2012, which claims the benefit of and priority to U.S. ProvisionalApplication Ser. No. 61/450,179 filed Mar. 8, 2011, the contents ofwhich are hereby incorporated by reference as if recited in full herein.

FIELD OF THE INVENTION

The invention relates to medical ribbons.

BACKGROUND OF THE INVENTION

It is believed that the linear organization of natural collagen fibersin tendons results in optimal stiffness and strength at low strainsunder tensile loads. However, this organization makes repairing rupturedor lacerated tendons difficult. Current suturing techniques to joinsplit ends of tendons, while providing sufficient mechanical strength toprevent gapping, are often inadequate to carry normal loads and may notever allow the tendon to regain original mechanical properties ormobility. Immobilization protocols used to restore tendon congruity mayresult in scar formation at the repair site and peripheral adhesionsthat can limit excursions. One or more similar issues may be associatedwith conventional ligament repair techniques.

SUMMARY OF EMBODIMENTS OF THE INVENTION

Embodiments of the invention are directed to medical ribbons. Theribbons include a woven ribbon body of a plurality of synthetic warp andweft collagen fiber yarns. The ribbon body has opposing first and secondend portions spaced apart in a length dimension connected bytransversely spaced apart first and second long sides defining a widthdimension.

The ribbon body can optionally include at least one suture woven intothe ribbon body and oriented to extend in a substantially straightlinear orientation along the length of the ribbon body. The at least onesuture can extend a length beyond both end portions of the ribbon body.

The ribbon body can optionally include some collagen fibers cross-linkedwith a first agent and some collagen fibers cross-linked with a second(different) agent to provide the respective fibers or yarns formed usingthose fibers with respective different mechanical properties and/ordegradation rate.

In some embodiments, the at least one suture is held only under weftyarns so that the at least one suture is visible on a first primarysurface of the ribbon body.

In some embodiments, the weft yarns crossover the at least one sutureonce about every 1 mm to about every 1 inch along the length of theribbon body.

The weft yarns can crossover the suture in a regular repeating patternover at least a major The at least one suture can be defined by aplurality of long collagen fiber warp yarns that have a length that isat least about 50% longer than other collagen fiber warp yarns of theribbon body. The tails of the long collagen fiber warp yarns can bebraided together outside the ribbon body.

The at least one suture can be a single suture that is attached to theribbon body proximate a longitudinally extending centerline of theribbon body.

The at least one suture can be a plurality of sutures, at least one ofwhich extends proximate each long side of the ribbon body.

The at least one suture can be four separate sutures, two each attachedto a respective long side of the ribbon body.

The synthetic collagen fibers comprise NDGA polymerized collagen fibers.

In some embodiments, some of the yarns comprise collagen fiberscross-linked with NDGA and other yarns comprise collagen fiberscross-linked with a different agent. For example, some of the yarnscomprise fibers cross-linked with NDGA and fibers cross-linked with adifferent agent.

The ribbon can have a greater number of warp yarns than weft yarns.

The at least one suture can include a suture comprising at least oneNDGA treated collagen fiber.

The at least one suture can be defined by four NDGA treated collagenfiber sutures, two each attached to a respective long side of the ribbonbody and the synthetic collagen fibers can include NDGA polymerizedcollagen fibers.

The different agent can be EDC and the EDC collagen fibers degradefaster than the NDGA collagen fibers.

The at least one suture can be defined by a plurality of NDGA treatedcollagen fiber yarns that define warp yarns along a length of the ribbonbody and have a length sufficient to extend outwardly therefrom todefine tail segments that have a length of between about 2 inches toabout 15 inches.

Still other embodiments are directed to methods of making a medicalribbon, including: (a) providing a plurality of discrete continuouslength synthetic collagen fibers; (b) braiding the fibers into yarns;(c) providing at least one suture; and (d) weaving the collagen fiberyarns together to form a ribbon body with a length while crossing weftyarns over a top of the suture at intervals along the length of theribbon to attach the at least one suture to the woven ribbon body anddefine at least one tail extension with a length of at least about 1inch that extends off at least one end of the ribbon body.

The weaving step can be carried out by attaching a single suture to theribbon body so that the single suture resides in a substantiallystraight line proximate a longitudinally extending centerline of theribbon body.

The providing step can be carried out to provide a plurality of sutures.The weaving step can be carried out to attach the plurality of suturesto the ribbon body so that at least one suture resides in asubstantially straight line proximate one long side of the ribbon bodyand at least one suture resides in a substantially straight lineproximate the other long side of the ribbon body.

The plurality of sutures can be four sutures, two on each respectivelong side of the ribbon body.

The weaving step can be carried out to have the weft yarns hold thesuture at discrete repeating segments along the length of the ribbonbody.

The synthetic fibers can include NDGA polymerized collagen fibers.

Some of the collagen fibers can be cross-linked with a first agent andsome of the collagen fibers can be cross-linked with a differentcross-linking agent to provide a different fiber tensile strength and adifferent intrabody degradation rate.

The at least one suture can be defined by a plurality of long warpcollagen fiber yarns with a length that is at least about 50% greaterthan other (shorter) warp collagen fiber yarns in the ribbon body. Thelonger yarns can be woven medially proximate a longitudinally extendingcenterline of the ribbon body to define two opposing tail ends.

Still other embodiments are directed to methods of making a medicalribbon, that include: (a) providing a plurality of collagen fiber warpyarns having a first length, each yarn comprising a plurality ofsynthetic collagen fibers; (b) providing a plurality of long collagenfiber warp yarns having a second length that is at least about 50%longer than the warp yarns first length, each long yarn comprising aplurality of synthetic collagen fibers; (b) providing a plurality ofcollagen fiber weft yarns, each yarn comprising a plurality of syntheticcollagen fibers; and (c) weaving the collagen fiber weft and warp yarnstogether to from a ribbon body using the long collagen fiber warp yarnsto define tails that extend beyond both ends of the ribbon body adistance of at least about 1 inch off at least one end of the ribbonbody.

The weaving step may be carried out using the long warp yarns assubstantially central warp yarns with warp yarns of the first (shorter)length on both sides thereof. The method may include braiding the tailsof the long warp yarns.

Still other methods are directed to repairing soft tissue. The methodsinclude: (a) placing a ribbon comprising synthetic collagen fibers andat least one integrated suture either: (i) held only by weft yarns ofthe ribbon over a length of the ribbon or (ii) defined by longercollagen warp fibers of the ribbon, such that lengths of the at leastone suture extend a distance beyond each end of the ribbon in apatient's body; and (b) attaching the at least one suture to localstructure to affix the ribbon in a desired position in the patient'sbody thereby repairing soft tissue in the patient's body.

It is noted that aspects of the invention described with respect to oneembodiment, may be incorporated in a different embodiment although notspecifically described relative thereto. That is, all embodiments and/orfeatures of any embodiment can be combined in any way and/orcombination. Applicant reserves the right to change any originally filedclaim or file any new claim accordingly, including the right to be ableto amend any originally filed claim to depend from and/or incorporateany feature of any other claim although not originally claimed in thatmanner. These and other objects and/or aspects of the present inventionare explained in detail in the specification set forth below.

Further features, advantages and details of the present invention willbe appreciated by those of ordinary skill in the art from a reading ofthe figures and the detailed description of the embodiments that follow,such description being merely illustrative of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a digital photograph of examples of ribbons of varying widthsand picks/inch (cross-over) of fibers used to form the medical ribbonsaccording to embodiments of the present invention.

FIG. 2A is a digital photograph of a portion of a ribbon with anintegrated suture according to embodiments of the present invention.

FIG. 2B is a digital photograph of a portion of a narrower ribbon withan integrated suture similar relative to the ribbon shown in FIG. 2Aaccording to embodiments of the present invention.

FIG. 3 is an enlarged digital photograph of a ribbon with a plurality ofintegrated sutures according to embodiments of the present invention.

FIG. 4A is a digital photograph of a narrow ribbon with an integratedsuture according to yet other embodiments of the present invention.

FIG. 4B is an enlarged close-up view of a portion of the narrow ribbonshown in FIG. 4A according to embodiments of the present invention.

FIGS. 5A and 5B are digital photographs of ribbons with pairs ofintegrated sutures on each long side of the ribbon according toembodiments of the present invention.

FIG. 6A is an enlarged view of a portion of the ribbon shown in FIG. 5A.

FIG. 6B is an enlarged view of a portion of the ribbon shown in FIG. 5B.

FIGS. 7A and 7B are view of end portions of ribbons similar to thoseshown in FIGS. 5A and 5B with different suture types according toembodiments of the present invention.

FIG. 8A is a digital photograph of ribbon with four independentintegrated sutures of #2 FiberWire® suture according to embodiments ofthe present invention.

FIG. 8B is an enlarged view of the ribbon shown in FIG. 8A.

FIGS. 9A-9D are digital photographs of an exemplary narrow ribbonaccording to embodiments of the present invention.

FIG. 10 is a schematic illustration of a flat ribbon with an integratedsuture configuration according to embodiments of the present invention.

FIG. 11 is a digital photograph of a ribbon (40 warp yarns) made fromcarbodiimide cross-linked collagen fibers according to some embodimentsof the present invention.

FIG. 12 is a flow chart of exemplary operations that can be used tocarry out embodiments of the present invention.

DETAILED DESCRIPTION

The present invention now is described more fully hereinafter withreference to the accompanying drawings, in which embodiments of theinvention are shown. This invention may, however, be embodied in manydifferent forms and should not be construed as limited to theembodiments set forth herein; rather, these embodiments are provided sothat this disclosure will be thorough and complete, and will fullyconvey the scope of the invention to those skilled in the art.

Like numbers refer to like elements throughout. In the figures, thethickness of certain lines, layers, components, elements or features maybe exaggerated for clarity. Broken lines illustrate optional features oroperations unless specified otherwise.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, elements,components, and/or groups thereof. As used herein, the term “and/or”includes any and all combinations of one or more of the associatedlisted items. As used herein, phrases such as “between X and Y” and“between about X and Y” should be interpreted to include X and Y. Asused herein, phrases such as “between about X and Y” mean “between aboutX and about Y.” As used herein, phrases such as “from about X to Y” mean“from about X to about Y.”

Unless otherwise defined, all terms (including technical and scientificterms) used herein have the same meaning as commonly understood by oneof ordinary skill in the art to which this invention belongs. It will befurther understood that terms, such as those defined in commonly useddictionaries, should be interpreted as having a meaning that isconsistent with their meaning in the context of the specification andrelevant art and should not be interpreted in an idealized or overlyformal sense unless expressly so defined herein. Well-known functions orconstructions may not be described in detail for brevity and/or clarity.

It will be understood that when an element is referred to as being “on”,“attached” to, “connected” to, “coupled” with, “contacting”, etc.,another element, it can be directly on, attached to, connected to,coupled with or contacting the other element or intervening elements mayalso be present. In contrast, when an element is referred to as being,for example, “directly on”, “directly attached” to, “directly connected”to, “directly coupled” with or “directly contacting” another element,there are no intervening elements present. It will also be appreciatedby those of skill in the art that references to a structure or featurethat is disposed “adjacent” another feature may have portions thatoverlap or underlie the adjacent feature.

It will be understood that, although the terms first, second, etc. maybe used herein to describe various elements, components, regions, layersand/or sections, these elements, components, regions, layers and/orsections should not be limited by these terms. These terms are only usedto distinguish one element, component, region, layer or section fromanother region, layer or section. Thus, a first element, component,region, layer or section discussed below could be termed a secondelement, component, region, layer or section without departing from theteachings of the present invention. The sequence of operations (orsteps) is not limited to the order presented in the claims or figuresunless specifically indicated otherwise.

The terms “implant” and “prosthesis” and “construct” are usedinterchangeably herein to designate an implantable product configured torepair, replace or supplement tissue such as at least a portion of anatural tendon, ligament, nerve, or other tissue of a mammalian subject(for veterinary or medical (human) applications). The term “implantable”means the device can be inserted, embedded, grafted or otherwisechronically attached or placed on or in a patient.

The term “about” means that the recited number can be more or less thanthe actual number, typically by about +/−20%, and more typically byabout +/−10%, of the respective number.

Collagen “microfibrils,” “fibrils,” “fibers,” and “natural fibers” referto naturally-occurring structures found in a tendon. Microfibrils areabout 3.5 to 50 nm in diameter. Fibrils are about 50 nm to 50 μm indiameter. Natural fibers are above 50 μm in diameter. A “syntheticfiber” refers to any fiber-like material that has been formed and/orchemically or physically created or altered from its naturally-occurringstate. For example, an extruded fiber of fibrils formed from a digestedtendon is a synthetic (collagen) fiber but a tendon fiber newlyharvested from a mammal is a natural fiber. Of course, syntheticcollagen fibers can include non-collagenous components, such asparticulates, hydroxyapatite and other mineral phases, or drugs thatfacilitate tissue growth. See, U.S. Pat. No. 6,821,530, herebyincorporated by reference herein. For example, the compositions cancontain carbon nano-tubes, zinc nano-wires, nano-crystalline diamond, orother nano-scale particulates; larger crystalline and non-crystallineparticulates such as calcium phosphate, calcium sulfate, apatiteminerals. For example, the fibers and/or constructs formed of the fiberscan include compositions can contain therapeutic agents such asbisphosphonates, anti-inflammatory steroids, growth factors such asbasic fibroblast growth factor, tumor growth factor beta, bonemorphogenic proteins, platelet-derived growth factor, and insulin-likegrowth factors; chemotactic factors such fibronectin and hyaluronan; andextracellular matrix molecules such as aggrecan, biglycan, and decorin.In some embodiments, the fibers and/or constructs can contain cells,engineered cells, stem cells, and the like, as well as combinations ofthe above.

The term “suture” refers to an elongate material that is used to attacha ribbon to a target anatomical structure to help hold the ribbon inlocation in or on the body. The suture may be resorbable ornon-resorbable, synthetic or natural. The suture can be configured tohold the implant in location for at least an initial post-implantationperiod of at least about 1 week, but may reside permanently in the bodyor, as noted above, may be substantially resorbable over time. Thesuture can be a single filament or multi-filament (braided or unbraided)thread, floss, gut or wire, or combinations thereof that can be used tohold a portion of an implant against or attached to target structures,typically to bone and/or tissue. The suture may comprise a resorbable ornon-resorbable biocompatible material. Examples of suture materialsinclude chromic gut (an absorbable, sterile surgical suture composed ofpurified connective tissue (mostly collagen)) derived from intestines,e.g., either the serosal layer of bovine or the submucosal fibrous layerof ovine intestines, cross-linked collagen fibers, polymeric materialsincluding, for example, polyester and nylon, elastomeric materials, suchas, for example, polymers, copolymers and/or derivatives thereof,including Vicryl®, as well as other materials including, for example,NITINOL, braided composite sutures including sutures with a multi-strandlong chain polyethylene core and a polyester braided jacket such asFiberWire® and combinations thereof. The suture may optionally be usedwith a suture anchor (bone or tissue anchor).

The term “flexible” means that the so-called member can be flexed orbent.

The term “woven” and derivatives thereof means a product that is formedusing warp and weft fibers woven in a manner that provides desiredmechanical properties for a particular application (e.g., rotator cuffrepair or ACL repair). The warp threads run lengthways of the piece ofcloth, and the weft runs across from side to side. The term “ribbon”refers to a substantially flat woven medical construct that isparticularly suitable for soft-tissue repair.

Optionally, it is also contemplated that, in some particularembodiments, the ribbons may be used as an external covering such as ascaffold to promote skin growth or an internal covering of animplantable device such as a pacemaker. In some embodiments, the ribboncan be used to help re-attach bone pieces such as a separated sternum orbone fractures.

FIG. 1 shows exemplary ribbons 10 of different widths and braidpatterns. The ribbons 10 can have any suitable number of yarns 10 y, anysuitable number of fibers 11 in each yarn, and/or any desired number ofpicks/inch to form the braid pattern. In some embodiments, the ribbons10 can have a substantially repeating weft pattern with a weft yarn(s)having a cross-over (a frequency) of about every .1 mm to about every 25mm, typically between about every 0.5-10 mm, and more typically in asubstantially repeating pattern with a cross over between about every1-5 mm.

Each yarn 10 y in a ribbon 10 can be a single fiber (also known asfilament) yarn or multi-fiber (multi-filament) yarn. Some yarns 10 y mayhave more fibers than others in a respective ribbon 10 or all the yarnsmay have the same number of fibers 11. The fiber 11 or fibers in eachyarn(s) 10 y may be twisted or untwisted, or combinations of twisted anduntwisted may be used for each or respective different yarns within asingle ribbon 10.

In some embodiments, the ribbons have a lesser number of weft yarnscompared to warp yarns and can be configured to provide a low-profilerelatively smooth ribbon body. The ribbons can have suitable warpdensity, weft density, ribbon count, ribbon weights and the like fordifferent uses.

In some embodiments, the yarns 10 y can each have between about 1-100elongate continuous length collagen fibers (treated to improve strength,such as treated with NDGA), typically between about 5-20 fibers in eachyarn 10 y. That is, the collagen fibers 11 can have a length sufficientto extend over substantially the entire length of the ribbon body. Theribbons 10 may have between about 1-1000 yarns, typically between about3-100 yarns some of which are weft and some of which are warp yarns. Forexample, the ribbon body 10 b can include between about 10-100 warpyarns 10 y of between about four to eight long NDGA treated collagenfibers 11 may be twisted or braided together for a respective yarn. Theribbon 10 shown in FIG. 2B illustrates 10 yarns of eight fibers each.The ribbon 10 shown in FIG. 11 includes 40 warp yarns; 8 braided fibersper yarn.

The ribbons 10 can be configured to have substantially the same physicalthickness and/or configuration as the replaced or repaired tissue so asto not cause discomfort or physical abnormalities in structure.

As desired, the body of the ribbon 10 can include a smooth outer sheaththat may be formed by a coating, gel or other material. In particularembodiments, the ribbon 10 can comprise polyglycolic acid, polylacticacid, or combinations of these or other substances.

In some embodiments, the ribbon 10 can have a length that is betweenabout 0.5-50 cm, typically between about 1-25 cm, and in someembodiments between about 2 cm to about 20 cm long. The ribbon 10 mayhave a width between about 0.05 to 8 cm, and is typically between about1-3 cm. The ribbon 10 may have a thickness of between about 0.01 toabout 30 mm, typically about 1-10 mm. The at least one suture 20 canextend at least about 1 inch off beyond each end of the ribbon body,typically between about 1-15 inches. The suture(s) 20 can be shorter onone end than the other (not shown).

The at least one suture 20 can be held only under weft yarns 10 y sothat the at least one suture is visible on a first primary (e.g., upperor lower flat) surface of the ribbon body 10 b. The weft yarns can crossover the at least one suture 20 as discussed above, such as, forexample, once about every 1 mm to about once every 1 inch along thelength of the ribbon body. The weft yarns 10 y can crossover the suture20 in a regular repeating pattern over at least a major portion of thelength of the ribbon body.

FIGS. 2A, 2B and 3 illustrate examples of ribbons 10 i with at least oneintegrated suture 20 that extends beyond at least one end of the ribbonbody 10 b, and typically beyond both ends of the ribbon body 10 b adistance of at least about 1 inch. The at least one suture 20 can bewoven into the weave of the ribbon body without requiring anysupplemental fixation members providing for a seamless smoothconfiguration. FIGS. 2A and 2B illustrate a single (multi-fiber) suture20 that is woven into an axially extending (lengthwise direction) centerportion of the ribbon body 10 and extends substantially straightthroughout the length of the ribbon body. Two or more (typicallysubstantially) parallel sutures oriented to extend in the lengthwisedirection may also be used instead of the single suture shown.

FIG. 3 illustrates that the ribbon 10 i can have at least twotransversely spaced apart sutures 20 that extend continuously andsubstantially equally spaced from an outer edge of respective long sidesof the ribbon 10 i over the entire length of the ribbon body 10 b. Twoor more substantially parallel sutures (one above the other) for each ofthe spaced apart sutures may also be used instead of the single sutureshown.

The suture 20 can comprise one or more suture yarns 20 y of a singlefiber 21 or multiple fibers 21, typically multiple synthetic collagenfibers 21, such as between about 2-100 elongate collagen fibers in arespective yarn 20 y. The suture yarn 20 y can be provided as twistedand/or braided fibers, or snugly held sets of parallel fibers or yarnsand/or sets of yarns 20 y.

FIG. 3 illustrates that the ribbon body 10 b of the integrated ribbon 10i can comprise two different types of collagen fibers, each cross-linkedwith a different chemical providing different mechanical properties suchas tensile strength and/or degradation or resorption properties. Thesuture yarn(s) 20 y can have a greater number of fibers than the ribbonyarns 10 y, typically at least about 50% more. The ribbons 10 i caninclude NDGA-cross linked multi-collagen fiber yarns 10 y (e.g., 8 fiberbraided yarns) forming the ribbon body, shown as the darker coloredfibers. The suture yarns 20 y can comprise 1-ethyl-3-(3-dimethylaminopropyl) -carbodiimide (EDC) cross linked multi-collagenfiber yarns, shown as the lighter color fibers (e.g., 16-fiber braidedyarns). The number of fibers in each yarn 10 y can vary depending on thetarget end use, typically between about 1-100 as noted above. In someembodiments at least some of the yarns 10 y in a particular ribbon body10 b can have between about 2-50 continuous length collagen fibers, suchas any number therebetween, including 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 45, 44, 45, 46, 47, 48,49, and 50.

FIG. 4A illustrates another example of a ribbon 10 i with an integratedsuture 20. In this embodiment, the ribbon body 10 b is relativelynarrow, and can have a width “W” that is less than about five (5) timesthe size of the suture 20. The suture 20 can be woven into the ribbonbody 10 b and extend axially over the entire ribbon body and extend adistance on each end outside the ribbon body. The extension lengths 20 ecan be at least about 30% of the length of the ribbon body, and in someembodiments may be about the same or greater than the length of theribbon body. FIG. 4B is a greatly enlarged view of one end of the ribbon10 i showing that the ribbon body may include a taper 10 t so that thebody tapers slightly inward to form a narrower portion proximate theextension segment 20 e of the suture. The taper 10 t can be the resultof the weave pattern and does not require any physical gluing orstitching at this junction. In other embodiments, the taper can be heldin its shape using a biocompatible adhesive. This weave attachment canprovide a smooth and seamless configuration of the suture 20 and ribbonbody 10 b. This configuration may be particularly suitable for rotatorcuff repairs.

FIGS. 5A and 5B illustrate examples of ribbons 10 i with transverselyspaced apart pairs of sutures 20 ₁, 20 ₂ and 20 ₃, 20 ₄ woven directlyinto the ribbon body 10 b, one pair proximate each opposing outer longside of the ribbon body 10 b. FIG. 6A is an enlarged view of a portionof the relatively long and more narrow ribbon 10 i shown in FIG. 5A, andFIG. 6B is an enlarged view of a portion of the relatively wide andshorter ribbon 10 i shown in FIG. 5B (e.g., typically about 5 cm longand about 1 to about 2 cm across or wide).

FIGS. 7A and 7B illustrate two different suture materials for pairs ofsutures (such as described above with respect to FIGS. 5A and 5B). FIG.7A illustrates that the sutures 20 can be continuous length NDGA treatedcollagen fibers while FIG. 7B illustrates polyester sutures.

FIG. 7A also illustrates that the sutures 20 do not appear on oneprimary surface of the ribbon body. This is because the ribbon 10 i canbe woven over a top of the suture(s) 20. This suture integration featurecan be true for all the embodiments discussed or shown herein.

FIGS. 8A and 8B illustrate an embodiment similar to that shown in FIGS.5A and 6A. As shown, the ribbon 10 i has four independent or separatesutures, typically two adjacent sutures proximate a respective outerlong side edge of the ribbon body. The sutures 20 ₁, 20 ₂ and 20 ₃, 20 ₄are woven to the ribbon body 10 b which, as shown, can have a relativelytight weave pattern. The ribbon body 10 b can be between about 3-8 mmwide, about 1 mm thick, and about 5-30 cm long. The cooperating pairs ofsutures can be used to affix the ribbon to local structure and mayprovide a more balanced fixation (torque resistant).

In some embodiments, the ribbon bodies 10 b and/or sutures 20 can beconfigured to have benign degradation. The term “benign degradation”means that the component degrades in the body without producing adverseor unnatural effects. For example, PLA sutures when degrading canproduce an acidic environment. The sutures 20 can consist essentially ofsynthetic collagen fibers that produce no such adverse effects.

In some embodiments, the ribbon bodies 10 b can be configured withtunable degradation. The term “tunable degradation” means that differentparts degrade in the body at different rates (e.g., break down atdifferent times). The word “tuning” refers to the fact that the ribboncomposition and/or fibers can be configured in a custom manner so thatdegradation can be specifically designed for different uses/sites. Thetunable degradation can be provided by cross-linking different collagenfibers with different agents. For example, some collagen fibers 11 canbe cross-linked with NDGA, while others can be cross-linked with adifferent agent, such as EDC or other cross-linking agent.

In yet other embodiments, three or more different cross-linking agentsmay be used to yield synthetic collagen fibers having differentproperties, including, for example, intrabody degradation time, tensilestrength and the like. For example, a first set of cross-linked collagenfibers 11 can be absorbed or resorbed by the body within about a firstday (e.g., 1-10 weeks, such as 1-4 weeks) range while a second set of(different) cross-linked fibers can be absorbed or resorbed by the bodywithin a longer day range (e.g., 6-52 weeks, such as between about 10-20weeks). The collagen fibers 11 of each cross-linked type may have thesame diameter or different diameters and collagen fibers of eachparticular cross-linked type may include fibers of different diameters.If the latter, for example, smaller cross-sectional/diameter NDGA fibers(e.g., about 0.1 mm or less, on average, dry) may have increasedstrength relative to thicker NDGA-treated fibers (e.g., about 0.15 mm orgreater, on average, dry).

In some embodiments, each yarn 10 y can be configured with collagenfibers 11, some of which are cross-linked with different cross-linkingagents than others. In other embodiments, each yarn 10 y can include thesame cross-linked fibers (of the same size).

In some embodiments, weft yarns can have the same cross-linked fiberswhile warp yarns can all have the same but different cross-linked fibersfrom the weft yarns. In other embodiments, some weft yarns can have afirst type of cross-linked fibers while others can have a different typeof cross-linked fibers. In some embodiments, some warp yarns can have afirst type of cross-linked fibers while others can have a different typeof cross-linked fibers. In some embodiments, only one type of warp orweft yarn can have a blend of different cross-linked fibers. In someembodiments, either the weft yarns or the warp yarns can have differentcross-linked collagen fibers while the other can be provided with thesame type of cross-linked fibers.

FIGS. 9A-9D illustrate yet another embodiment of a ribbon 10 with anintegrated suture 20. In this embodiment, the ribbon 10 is formed of 100percent collagen fibers. That is, the ribbon body 10 b and suture 20 areboth formed of only elongate lengths of collagen fiber yarns 10 y, 20 y,each yarn including multiple collagen fibers. The suture yarns 20 y arelonger than the ribbon body warp yarns 10 y, typically at least about50% longer, so as to extend outward between about 2-20 inches on eachend of the ribbon body 10 b to form extensions 20 e (also referred to as“tails”) that can be used for attachment to local soft tissue and/orbone. The suture collagen yarns 20 y can be pre-braided fibers and/orpre-braided yarns that are then woven into the ribbon body 10 b. Thesuture yarns 20 y can form a single braided warp suture yarn in theribbon body 10 b or, a multiple braided suture yarns in the woven ribbonbody 10 b. In some embodiments, the suture yarns 20 y comprise multipletwisted or braided collagen fibers and define at least two (shown asthree) warp yarns of the ribbon body. However, outside the ribbon body,the suture yarns can be braided together to form the extensions or tails20 e.

FIG. 10 illustrates that the suture yarns 20 y can comprise a pluralityof warp yarns 20warp that define some of the ribbon body warp yarns10warp and extend along a center of the ribbon body 10 b with shorterwarp ribbon yarns 10 y on each side thereof (shown as five warp yarns oneach side of the suture yarns 20 y, but less or more may be used). Theribbon body 10 b also includes weft yarns 10weft. As shown, there arethree braided multi-fiber collagen yarns 20 y that form the suture tails20 e and these yarns can be the same or a different size from the ribbonbody yarns 10 y. Each ribbon body yarn 10 y can include a plurality ofcollagen fibers, typically between about 3-20, and more typicallybetween about 5-10, and in particular embodiments, about 8 long collagenfibers.

FIG. 11 illustrates the ribbon 10 can include one or more (shown ashaving a sinusoidal shape) weft yarns 10weft that has a frequency, onaverage, of about 5 mm (from peak to peak or base to base). In thisembodiment, there are about 40 warp yarns 10warp and each yarn may havea plurality of fibers (e.g., 4-20 braided fibers per yarn, typicallyabout 8 as shown). In this embodiment, the fibers are all collagenfibers cross-linked with carbodiimide.

FIG. 12 illustrates some operations that can be used to carry outembodiments of the invention. Continuous lengths of synthetic collagenfibers are provided (block 100). A plurality of the collagen fibers arebraided or twisted together to form collagen yarns (block 110). Thecollagen yarns are woven as a set of weft and warp yarns to form aribbon (block 120). At least one elongate suture can be woven overribbon yarns or as warp yarns in the ribbon body to provide (a straightlengthwise oriented) integrated suture that extends over the entirelength of the ribbon body and extends outward a distance from both endsof the ribbon body (block 130).

Each of the collagen fibers can be cross-linked with the same or adifferent agent (block 102), such as NDGA. At least some of the collagenfibers can be cross-linked with NDGA while others can be cross-linkedwith another non-toxic agent (block 105). The at least one suture caninclude least one collagen fiber, thereby providing a more benignintrabody degradation relative to PLA and VICRYL sutures (block 125).

In some embodiments, the method can include tuning a degradation cycleof the ribbon by using different materials to form the ribbon bodyand/or suture(s) (block 108).

The weaving of the at least one suture can be carried out by weaving atleast two spaced apart collagen fibers into the ribbon body alongopposing long sides of the ribbon body (block 127). In some embodiments,the weaving of the at least one suture can be carried out by weavingfour separate sutures (over one primary surface of the ribbon bodyyarns), two sutures on each long side of the ribbon body (block 129).The weaving can include weaving long collagen yarns as warp yarns of theribbon body and braiding tail portions of the long collagen yarnstogether outside the ribbon body (block 128).

Also, the ribbon body and/or suture(s) can optionally be coated,impregnated and/or amalgamated with a gel or other material. The coatingmay be to promote fibroblasts, and/or comprise one or more of ananti-inflammatory agent, an antibiotic or other therapeutic agent.

The ribbon body 10 b and/or sutures(s) 20 are biocompatible and may beabsorbed, resorbed and/or biodegradeable over time.

The ribbon body can be configured to have similar or greater tensilestrength, stiffness and dynamic flexibility as corresponding naturaltissue, e.g., natural ligament or tendon fibers. Embodiments of theinvention may be particularly suitable for augmenting, repairing orreplacing tendons and ligaments.

In some embodiments, the fibers comprise any collagen fibers formed inany suitable manner to be acceptable as a biomedical implant/construct.

In particular embodiments, the fibers can comprise NDGA-treatedcollagen. Suitable ways of forming NDGA polymerized and/or treatedfibers are described in U.S. Pat. Nos. 6,565,960 and 6,821,530, thecontents of which are hereby incorporated by reference as if recited infull herein. Generally stated, bulk collagen can be solubilized bydigestion with a protease, then extruded into a synthetic fiber.Properly processed NDGA polymerized fibers are biocompatible. After thepolymerization process, the fibers can be washed in ethanol andphosphate buffered saline to remove cytotoxins due to leachable reactionproducts. For additional discussion of the NDGA polymerized fibers, see,Thomas J. Koob, Biomimetic approaches to Tendon Repair, ComparativeBiochemistry and Physiology Part A 133 (2002) 1171-1192. See also,co-pending U.S. Provisional Application Ser. No. 61/422,363 (AttorneyDocket No. 9624-25PR2), the contents of which are hereby incorporated byreference as if recited in full herein.

Generally stated, to make the collagen fibers, preparatory donorcollagen material can be pepsin-derived or solubilized collagen that isprocessed/purified. The purified collagen preparatory material isdialyzed a plurality of times in a selected liquid for a desired periodof time. The dialyzing is typically repeated three times. The dialyzingcan be carried out against dionized (DI) water in a volume ratio ofbetween about 30:1 to about 100:1, typically about 60 to 1, for betweenabout 30-90 minutes, typically about 40 minutes. The dialyzing can forma substantially clear gel of collagen fibrils indicating goodorganization (substantially parallel fibrils), where opacity indicatesless organization. The organization can help improve tensile strength ofsubsequently cross-linked fibers.

The dialyzed collagen material can be incubated for a desired timebefore placing in a fiber-forming buffer. The dialyzed gel can becross-linked to provide collagen fibers for medical constructs. Thepolymerization (e.g., cross-linking) can be carried out using NDGA andthe resultant NDGA treated collagen fibers can be relatively thin, suchas, for example, about 0.08 mm dry diameter (on average).

The incubation may be for at least about 24 hours, typically 24-48hours, and may be at room temperature of between about 15-30° C.,typically about 25° C. The dialysis process can be used beforecross-linking for subsequent use with any suitable cross-linkingmaterials, to promote collagen organization, such as, for example, andthe process is not limited to NDGA, but may be useful with othermaterials, including, for example, glutaraldehyde. For additionaldiscussion of methods used to form high-strength NDGA treated collagenfibers, see, U.S. application Ser. No. 11/964,756, the contents of whichare hereby incorporated by reference as if recited in full herein.

The foregoing is illustrative of the present invention and is not to beconstrued as limiting thereof Although a few exemplary embodiments ofthis invention have been described, those skilled in the art willreadily appreciate that many modifications are possible in the exemplaryembodiments without materially departing from the novel teachings andadvantages of this invention. Accordingly, all such modifications areintended to be included within the scope of this invention as defined inthe claims. The invention is defined by the following claims, withequivalents of the claims to be included therein.

1. A method of repairing soft tissue, comprising: placing a ribbon comprising synthetic collagen fibers and at least one integrated suture either (i) held only by weft yarns of the ribbon over a length of the ribbon or (ii) defined by longer collagen warp fibers of the ribbon, such that lengths of the at least one suture extend a distance beyond each end of the ribbon in a patient's body; and attaching the at least one suture to local structure using the extending lengths to affix the ribbon in a desired position in the patient's body thereby repairing soft tissue in the patient's body.
 2. The method of claim 1, wherein the attaching and placing steps are carried out to repair a tendon or a ligament. 